Study Raises Questions About Digoxin Use Today

Digitalis is one of the oldest medicines in the cardiovascular arsenal. When William Withering identified digitalis as the active ingredient in the foxglove plant more than 200 years ago he was only codifying a longstanding folk remedy for heart failure, or "dropsy" as it was known then.

Digitalis fully entered the modern era with the publication of the DIG trial in 1997. The trial found that digitalis reduced hospitalization for heart failure but did not have an impact on mortality. On the basis of the trial digitalis received recommendations in the US and European guidelines for use in patients with systolic heart failure who remain symptomatic despite optimal therapy. However, the epidemiology and treatment of heart failure have evolved considerably since then. Now the authors of a new study, supported by an accompanying editorial, say that these recommendations need to be reconsidered.

After adjusting for other factors the increase in mortality, but not the increase in hospitalization, remained significant:

Digoxin hazard ratio for mortality: 1.72, CI 1.25–2.36

Digoxin hazard ratio for hospitalization: 1.05, CI 0.82–1.34

The overall findings were consistent for both men and women and for people taking beta-blockers and for people not taking beta-blockers.

The authors acknowledged that because they performed an observational study they were unable to demonstrate a direct cause-and-effect related to digoxin. However, they pointed out that since the DIG trial"substantial improvements in HF treatment have occurred," including increased use of beta-blockers,
ACE inhibitors, ARBs, and aldosterone antagonistsm which "may substantially modify the independent effect of digoxin on death and HF hospitalization." They write that their "community-based systolic HF cohort is more likely to represent patients with systolic HF in the modern era with regard to pathogenesis and treatment patterns." They recommend that the use of digoxin for systolic heart failure should be "re-evaluated."

In an accompanying editorial, Lionel Opie writes that the new study "is of considerable importance" because the evidence base for the current use of digoxin is "highly unsatisfactory." He agrees with the study authors that it is time to "seriously question" the US and European guidelines that support the current use of digoxin.